This research concerns the role in the neoplastic response of mice to skin painting with 3-methylcholanthrene (MCA) of the response to acute viral infection and to endogenous infection by murine leukemia virus (MuLV) and of whether the carcinogen induces or not the enzyme Aryl Hydrocarbon Hydroxylase (AHH). The induction of skin tumors by MCA painting. A high incidence of these tumors has been observed only in inbred and hybrid mice in which: the carcinogen induces low or no leukemia and induces AHH; the skin is highly susceptible to vaccinia infection which in turn enhances the skin neoplastic response to the carcinogen; MuLV is very low or not detectable. The inbred mice include the BALB/c, C3HeB/Fe, A, CBA and MA. The induction of leukemia by MCA painting. A high incidence of these leukemias has been observed only in inbred and hybrid mice in which: the carcinogen induces few or no skin tumors and does not induce AHH; the skin is only very weakly susceptible or resistant to vaccinia virus; MuLV is restricted or not detectable. The inbred mice include the RF/J, DBA/1, DBA/2 and, though less susceptible to the leukemias, the 129 and St/b. High spontaneous leukemia is associated with a high level of MuLV and can occur in AHH noninducible mice (AKR) and in AHH inducible mice (C58); in the latter the high level of MuLV seems to inhibit the induction of skin tumors by MCA painting.